Thoughts and Suggestions on Safety Evaluation of Combined use of Traditional Chinese Medicine in Clinical Research

doi:10.19803/j.1672-8629.2021.01.02

Abstract

Abstract: Objective To study methods for safety evaluation of combined use of traditional Chinese medicine in clinical research in order to meet the needs of clinically safe and effective medication.Methods Starting with the clinical study of Traditional Chinese medicine,this paper analyzes the problems with the safety of combined use of traditional Chinese medicine in clinical study,and offers solutions to the major problems.Results A safety evaluation system for drug combination of TCM and Western medicine needed to be established and improved.Conclusion The safety evaluation of drug combination of TCM and Western medicine should start with the early stage of development and run through the life cycle of new drugs from clinical trial to post-marketing evaluation.Importance should be attached to research design and risk-benefit assessment.A dynamic research model of research design-monitoring evaluation-analysis prediction-risk management is to be adopted,and a multidisciplinary comprehensive assessment system established.

Key words: traditional Chinese medicine(TCM), clinical research, drug combination, drug-drug interaction(DDI), safety evaluation

CLC Number:

R288R969.3

CHENG Jinlian, OUYANG Huitian, JIN Hongtao, ZHU Xueqi, XIAO Shuang, LEI Xiang, GAO Chunsheng, LIU Qingquan. Thoughts and Suggestions on Safety Evaluation of Combined use of Traditional Chinese Medicine in Clinical Research[J]. Chinese Journal of Pharmacovigilance, 2021, 18(1): 4-10.

References

[1] Li H,Shen KK.Research progress of drug combination of Chinese materia medica on antitumor[J],Academic Journal of Shanghai University of Traditional Chinese Medicine(上海中医药大学学报),2017,31(3):90-94.
[2] Zheng CX,Zheng XY,Kong LX,et al.Potential medication risk analysis of Chinese patent medicine in the treatment of stable chronic obstructive pulmonary disease[J].China Pharmacy(中国药房),2020,31(7):841-844.
[3] Yang XB,Li XH,Wang F,et al.Research progress of traditional Chinese medicine intervention in septic shock[J].Yunnan Journal of Traditional Chinese Medicine and Materia Medica(云南中医中药杂志),2019,40(7):68-70.
[4] Hong F,Teng L,He JC.Research progress of interaction between Chinese medicine and western medicine in treatment of chronic heart failure[J].Chinese Journal of Cardiovascular Rehabilitation Medicine(心血管康复医学杂志),2020,29(2):253-255.
[5] Poonam T,Prakash GP,Kumar LV.Influence of Allium sativum extract on the hypoglycemic activity of glibenclamide:an approach to possible herb-drug interaction[J].Drug Metabol Drug Interact,2013,28(4):225-30.
[6] Fu H,Rong YH,Wang L.Rationality evaluation of traditional Chinese medicine injections for promoting blood circulation in patients with cerebral infarction in Jiangsu Province Hospital of Chinese Medicine from 2017 to 2018[J].Drugs &Clinic(现代药物与临床) ,2020,35(1):154-159.
[7] Zhuang W,Sun N,Wang J,et al.Role and experience of clinical pharmacist in the combination of warfarin and traditional Chinese medicine[J].China Pharmacist(中药临床药学),2019,22(6):1072-1075,1087.
[8] Jiang YN.Clinical analysis of 160 patients with drug-induced liver injury[J].Medical Journal of Chinese People's Health(中国民康医学),2019,31(22):111-112.
[9] Singh A,Zhao K,Bell C,et al.Effect of berberine on in vitro metabolism of sulfonylureas:A herb-drug interactions study[J].Rapid Communications in Mass Spectrometry,2019,34(S4):e8651.
[10] Li H,Yang C,Jin H.Recent research progress in mechanism of liver injury induced by common drugs[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2019,16(12):750-756.
[11] National Center for ADR Monitoring,China.2019 Annual report for national ADR monitoring[EB/OL].(2020-04-10)[2020-09-09].http://www.cdr-adr.org.cn/drug_1/aqjs_1/drug_aqjs_sjbg/202004/t20200420_47318.html.
[12] Huang T.Analysis of adverse drug reactions of 387 cases induced by Traditional Chinese Medicine Injections in Kunshan city[J].Journal of Modern Medicine &Health(现代医药卫生),2019,35(11):1643-1646.
[13] National Administration of Traditional Chinese Medicine.Guiding principles for clinical application of Chinese patent medicine[EB/OL].(2010-06-30)[2020-09-09].http://www.satcm.gov.cn/yizhengsi/gongzuodongtai/2018-03-24/3071.html.
[14] Brown AC.Liver toxicity related to herbs and dietary supplements:Online table of case reports Part 2 of 5 series[J].Food Chem Toxicol,2017,107(Pt A):472-501.
[15] Shuting Wang,Wanfang Li,Jianbo Yang,et al.Research progress of herbal medicines on drug metabolizing enzymes:consideration based on toxicology[J].Current Drug Metabolism ,2020,21:1-15.
[16] Hao JX,Zhang HD,Xiong KP,et al.Randomized controlled clinical trial of felodipine tablets combined used with tianmagouteng granules on treating hypertension[J/OL].Journal of Practical Traditional Chinese Internal Medicine(实用中医内科杂志).http://kns.cnki.net/kcms/detail/21.1187.r.20200310.1940.031.html.
[17] Liu QL,Gong QJ,Yu XY.Application of traditional Chinese medicine in drug application of traditional Chinese medicine in drug combination for coronary heart disease[J].Technology and Enterprise(科技与企业) ,2014(8):286-287.
[18] Guo JY,Huo HR,Jiang TL.Evaluation of research methods to measure the effects of combined drugs[J].Pharmacology and Clinics of Chinese Materia Medica(中药药理与临床),2005,21(3):60-64.
[19] ICH.M3(R2) Guidance on nonclinical safety studies for the conduct of human clinical trials and marketing authorization for pharmaceuticals[EB/OL].(2009-06-11)[2020-09-09].https://database.ich.org/sites/default/files/M3_R2__Guideline.pdf.
[20] Center for drug evaluation,NMPA of China.Technical guidelines for drug interaction research (exposure draft)[EB/OL].(2020-09-11)[2020-09-25].http://www.cde.org.cn/news.do?method=largeInfo&id=a24d50a14e59b266.
[21] Center for drug evaluation,NMPA of China.Technical guidelines for clinical trials of combination therapy with antitumor agents(exposure draft)[EB/OL].(2020-07-17)[2020-09-09].http://www.cde.org.cn/news.do?method=largeInfo&id=5d938422a5c1c7e6.
[22] Zhu XQ,Cheng JL,Liu QQ.Thoughts on the registration of new traditional Chinese medicines in the COVID-19 epidemic situation[J].Chinese Journal of New Drugs (中国新药杂志),2020,29(16):1813-1817.
[23] Lu S.Introduction of guidance for clinical evsluation of an ti-rheumatic drugs in Japan[J].Chin J Clin Pharmacol(中国临床药理学杂志) ,2010,26(8):634-640.
[24] Dong H,Ma J,Li T,et al.Global deregulation of ginseng products may be a safety hazard to warfarin takers:solid evidence of ginseng-warfarin interaction[J].Scientific Reports,2017,7(1):5813
[25] Mohutsky MA,Anderson GD,Miller JW,et al.Ginkgo biloba:evaluation of CYP2C9 drug interactions in vitro and in vivo[J].AmJ Ther,2006,13(1):24-31.
[26] Matthews MK,Jr,Association of Ginkgo biloba with intracerebral hemorrhage[J],Neurology,1998,50(6) 1933-1934.
[27] Tian Z,Pang H,Du S,et al.Effect of Panax notoginseng saponins on the pharmacokinetics of aspirin in rats[J].J Chromatogr B Analyt Technol Biomed Life Sci,2017,1040:136-143.
[28] Zhou L,Wang S,Zhang Z,et al.Pharmacokinetic and pharmaco-dynamic interaction of Danshen-Gegen extract with warfarin and aspirin[J].J Ethnopharmacol,2012,143(2):648-55.
[29] Chen X,Jin J,Chen Y,et al.Effect of scutellarin on the metabolism and pharmacokinetics of clopidogrel in rats[J].Biopharm Drug Dispos,2015:36(1):64-8.
[30] Li X,Chen C,Chen QQ,et al.An in vitro study on metabolic interaction between main active components of Salviae Miltiorrhizae Radix et Rhizoma and tacrolimus[J/OL].China Journal of Chinese Materia Medica(中国中药杂志).https://doi.org/10.19540/j.cnki.cjcmm.20200715.201.
[31] U.S.Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER).In Vitro Drug Interaction Studies-Cytochrome P450 Enzyme-and Transporter-Mediated Drug Interactions Guidance for Industry[EB/OL].(2020-01)[2020-09-09].https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs.
[32] Center for drug evaluation,NMPA of China.Safety information evaluation and management during drug clinical trials (trial)[EB/OL].(2020-07-01)[2020-09-09].http://www.cde.org.cn/news.do?method=largeInfo&id=938b81c153eaf85e.
[33] U.S.Department of Health and Human Services Food and Drug Administration Center for Drug Evaluation and Research (CDER).Clinical Drug Interaction Studies-Cytochrome P450 Enzyme- and Transporter-Mediated Drug Interactions Guidance for Industry[EB/OL].(2020-06)[2020-09-09].https://www.fda.gov/drugs/guidance-compliance-regulatory-information/guidances-drugs.
[34] ICH.E2C(R2) Periodic Benefit-Risk Evaluation Report (PBRER)[EB/OL].(2012-12-17)[2020-09-09].https://database.ich.org/sites/default/files/E2C_R2_Guideline.pdf.
[35] Lv J,Xie YM,Wang ZF,et al.Real world study on characteristics of Maixuekang capsules combined with traditional Chinese medicines in treating nephrotic syndrome[J],China journal of Chinese Materia Medica(中国中药杂志) ,2019,44(8):1668-1673.
[36] Mo K,Nong L,Cao W,et al.Research on adverse drug reaction monitoring based on Chinese hospital pharmacovigilance system[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2020,17(10):672-675.
[37] Shen CY,Wu TT,Liu W,et al.Post-marketing surveillance and evaluation of Chinese drugs in the new era[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2020,17(10):649-652,675.
[38] National Medical Products Administration of China.Guidelines for the collection and reporting of adverse drug reactions in individual cases[EB/OL].(2018-12-31)[2020-09-09].https://www.nmpa.gov.cn/xxgk/ggtg/qtggtg/20181221172901438.html.
[39] Chen JJ,Qian PP,Cao K,et al.Comparison and analysis of causality assessment method in China and naranjo's method in the evaluation of adverse drug reactions[J].Chinese Pharmaceutical Affairs(中国药事),2020,34(8):988-992.
[40] Zhang XL,Shen XK,Huang YY.Clinical analysis of 130 cases of drug-induced liver injury in cancer patients[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2020,17(9):589-593.
[41] Yu Y.Adverse drug reaction knowledge integration and application research based on big data mining[D].Changchun:Jilin University(吉林大学) ,2016.
[42] Lyu TY,Kuang L,Chen MY.Analysis of 1073 cases of clinical use of reduning injection by Pareto chart and fishbone diagram[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2020,17(10):745-748.
[43] Wang XJ,Fang QY,Wei HJ.Pareto chart analysis on 96 cases of adverse reactions of Chinese patent medicine[J].China Pharmaceuticals(中国药业),2020,29(18):22-26.
[44] Zhu MJ,Zhang DD,Yang Y,et al.Efficacy and safety of oral snticoa--gulants in non-valvular atrial fibrillation therapy:a bayesian network meta-analysis[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2020,17(10):726-731.
[45] Wang M,Guo XJ,Ye XF,et al.Application of bayesian instrumental variable in active surveillance data of adverse drug reactions:a simulation study[J].Chinese Journal of Pharmacovigilance(中国药物警戒),2019,16(3):139-143.
[46] Zang WX.Network technology was used to analyze the adverse reactions caused by cephalosporins combined with many western medicines[J].China New Telecommunications(中国新通信),2020,22(16):228.
[47] Li Q,Jin XY,Zhou X,et al.Analysis of differences between different research types in clinical safety evaluation of Xue bijing Injection[J/OL].China Journal of Chinese Materia Medica(中国中药杂志).https://doi.org/10.19540/j.cnki.cjcmm.20200715.201.
[48] Cheng JQ,Shi QP,Jiang XD,et al.Meta-analysis of incidence rates and influencing factors of adverse drug reactions related to salvianolate injection[J].ChineseJournal of Modern Applied Pharmacy(中国现代应用药学),2020,37(11):1355-1364.
[49] Wang M.Research and application of bayesian instrumental variable in active surveillance of adverse drug reaction[D].Xi’an:The Second Military Medical University,2019.